Department of Biochemistry, The Laboratory for Evolution and Development, The University of Otago, Dunedin 9054, Aotearoa-New Zealand.
Department of Genetics and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria, Australia.
Pest Manag Sci. 2018 Jul;74(7):1616-1622. doi: 10.1002/ps.4852. Epub 2018 Feb 26.
Nitenpyram is a member of the economically important neonicotinoid class of insecticides. The in vivo metabolism of nitenpyram is not well characterised, but cytochrome P450 activity is the major mechanism of resistance to neonicotinoids identified in insect pests, and P450s metabolise other neonicotinoids including imidacloprid.
Here, we used the GAL4-UAS targeted expression system to direct RNA interference (RNAi) against the cytochrome P450 redox partners to interrupt P450 functions in specific tissues in Drosophila melanogaster. RNAi of the mitochondrial redox partner defective in the avoidance of repellents (dare) in the digestive tissues reduced nitenpyram mortality, suggesting an activation step in the metabolism of nitenpyram carried out by a mitochondrial P450. RNAi of the mitochondrial cytochrome P450 Cyp12a5, which is expressed in the digestive tissues, resulted in the same phenotype, and transgenic overexpression of Cyp12a5 increased nitenpyram sensitivity.
These results suggest that in vivo metabolism of nitenpyram by the mitochondrial P450 CYP12A5 results in the formation of a product with higher toxicity than the parent compound. © 2018 Society of Chemical Industry.
吡虫啉是具有重要经济意义的新烟碱类杀虫剂的一员。吡虫啉在体内的代谢尚未得到很好的描述，但细胞色素 P450 活性是昆虫对新烟碱类杀虫剂产生抗性的主要机制，而 P450 还代谢其他新烟碱类杀虫剂，包括吡虫啉。
在这里，我们使用 GAL4-UAS 靶向表达系统，针对特定组织中的细胞色素 P450 氧化还原伴侣进行 RNA 干扰（RNAi），以干扰果蝇中的 P450 功能。在消化组织中 RNAi 靶向线粒体氧化还原伴侣逃避驱虫剂缺陷（dare）降低了吡虫啉死亡率，这表明吡虫啉代谢的激活步骤是由线粒体 P450 完成的。在消化组织中表达的线粒体细胞色素 P450 Cyp12a5 的 RNAi 导致了相同的表型，并且 Cyp12a5 的转基因过表达增加了吡虫啉的敏感性。
这些结果表明，体内代谢吡虫啉通过线粒体 P450 CYP12A5 形成了比母体化合物毒性更高的产物。© 2018 化学工业协会。
